Treatment of Patients With Schizophrenia

Last updated May 27, 2022

Introduction

Introduction

  • The lifetime prevalence of schizophrenia is estimated to be approximately 0.7%. Worldwide, schizophrenia is one of the top 20 causes of disability.
  • Schizophrenia is also associated with increased mortality, with a shortened lifespan and standardized mortality ratios that are reported to be twofold to fourfold those in the general population. Individuals often have physical health comorbidities such as cardiovascular, respiratory, and infectious diseases and malignancies, particularly lung cancer.
  • About 4%–10% of persons with schizophrenia die by suicide, with rates that are highest among males in the early course of the disorder. Additional causes of death also include other unnatural events such as accidents and traumatic injuries.
  • Harms from therapeutic interventions may include:
    • adverse events that range from serious to less serious but affect tolerability to minor
    • negative effects of the intervention on quality of life
    • barriers and inconveniences associated with treatment
    • other negative aspects of treatment that may influence decision-making by the patient, the clinician or both.
  • The guideline statements should be implemented in the context of a person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments for schizophrenia.
  • See full text guideline for additional information.

Assessment

Assessment

Note: none of the subsequent statements are meant to stand alone.


As outlined in APA’s Practice Guidelines for the Psychiatric Evaluation of Adults (3rd edition), APA recommends that the initial assessment of a patient with a possible psychotic disorder include:
  • the reason the individual is presenting for evaluation
  • the patient’s goals and preferences for treatment
  • a review of psychiatric symptoms and trauma history
  • an assessment of tobacco and other substance use
  • a psychiatric treatment history
  • an assessment of physical health
  • an assessment of psychosocial and cultural factors
  • a mental status examination, including cognitive assessment
  • an assessment of risk of suicide and aggressive behaviors.
(1, C)
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APA recommends that the initial psychiatric evaluation of a patient with a possible psychotic disorder include a quantitative measure to identify and determine the severity of symptoms and impairments of functioning that may be a focus of treatment. (1, C)
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APA recommends that patients with schizophrenia have a documented, comprehensive, and person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments. (1, C)
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Figure 1. Managing Schizophrenia


Suggested physical and laboratory assessments for patients with schizophrenia

Assessment Initial or baselinea Follow-upb
Assessments to monitor physical status and detect concomitant physical conditions
Vital signs Pulse, blood pressure Pulse, blood pressure, temperature as clinically indicated
Body weight and height Body weight, height, BMIc BMIc every visit for 6 months and at least quarterly thereafter
Hematology CBC, including ANC CBC, including ANC if clinically indicated (e.g., patients treated with clozapine)
Blood chemistries Electrolytes, renal function tests, liver function tests, TSH As clinically indicated
Pregnancy Pregnancy test for women of childbearing potential
Toxicology Drug toxicology screen, if clinically indicated Drug toxicology screen, if clinically indicated
Electrophysiological studies EEG, if indicated on the basis of neurological exam or history
Imaging Brain imaging (CT or MRI, with MRId being preferred), if indicated on the basis of neurological exam or history
Genetic testing Chromosomal testing, if indicated on the basis of physical examination or history, including developmental historye
Assessments related to other specific side effects of treatment
Diabetesf Screening for diabetes risk factors,g fasting blood glucoseh Fasting blood glucose or hemoglobin A1C at 4 months after initiating a new treatment and at least annually thereafterh
Hyperlipidemia Lipid paneli Lipid paneli at 4 months after initiating a new antipsychotic medication and at least annually thereafter
Metabolic syndrome Determine whether metabolic syndrome criteria are metj Determine whether metabolic syndrome criteria are metj at 4 months after initiating a new antipsychotic medication and at least annually thereafterj
QTc prolongation ECG before treatment with chlorpromazine, droperidol, iloperidone, pimozide, thioridazine, or ziprasidonek or in the presence of cardiac risk factorsl ECG with significant change in dose of chlorpromazine, droperidol, iloperidone, pimozide, thioridazine, or ziprasidone, or with the addition of other medications that can affect kQTcl interval in patients with cardiac risk factors or elevated baseline QTc intervals
Hyperprolactinemia Screening for symptoms of hyperprolactinemiam
Prolactin level, if indicated on the basis of clinical history
Screening for symptoms of hyperprolactinemia at each visit until stable, then yearly if treated with an antipsychotic known to increase prolactinm
Prolactin level, if indicated on the basis of clinical history
Antipsychotic-induced movement disorders Clinical assessment of akathisia, dystonia, parkinsonism, and other abnormal involuntary movements, including tardive dyskinesian
Assessment with a structured instrument (e.g., AIMS, DISCUS) if such movements are present
Clinical assessment of akathisia, dystonia, parkinsonism, and other abnormal involuntary movements, including tardive dyskinesia, at each visitn
Assessment with a structured instrument (e.g., AIMS, DISCUSo) at a minimum of every 6 months in patients at high risk of tardive dyskinesia and at least every 12 months in other patientsp as well as if a new onset or exacerbation of preexisting movements is detected at any visit
See full text guideline for additional important information in footnotes.

Treatment

Treatment

Pharmacotherapy

APA recommends that patients with schizophrenia be treated with an antipsychotic medication and monitored for effectiveness and side effects.*

The choice of medication should consider:

  • addressing patient's non- or partial response
  • side-effect profile
  • presence of other health conditions that may be affected by medication side effects
  • formulations
  • interactions and metabolism
  • pharmacokinetic properties
(1, A)
See full text guideline for more information.
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APA recommends that patients with schizophrenia whose symptoms have improved with an antipsychotic medication continue to be treated with an antipsychotic medication.* (1, A)
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APA recommends that patients with schizophrenia whose symptoms have improved with an antipsychotic medication continue to be treated with an antipsychotic medication.* (1, A)
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APA suggests that patients with schizophrenia whose symptoms have improved with an antipsychotic medication continue to be treated with the same antipsychotic medication.* (2, B)
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APA recommends that patients with treatment-resistant schizophrenia be treated with clozapine.* (1, B)
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APA recommends that patients with schizophrenia be treated with clozapine if the risk for suicide attempts or suicide remains substantial despite other treatments.* (1, B)
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APA suggests that patients with schizophrenia be treated with clozapine if the risk for aggressive behavior remains substantial despite other treatments.* (2, C)
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APA suggests that patients receive treatment with a long-acting injectable antipsychotic medication if they prefer such treatment or if they have a history of poor or uncertain adherence.* (2, B)
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APA recommends that patients who have acute dystonia associated with antipsychotic therapy be treated with an anticholinergic medication. (1, C)
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APA suggests the following options for patients who have parkinsonism associated with antipsychotic therapy: lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, or treating with an anticholinergic medication. (2, C)
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APA suggests the following options for patients who have akathisia associated with antipsychotic therapy: lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, adding a benzodiazepine medication, or adding a beta-adrenergic-blocking agent. (2, C)
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APA recommends that patients who have moderate to severe or disabling tardive dyskinesia associated with antipsychotic therapy be treated with a reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2). (1, B)
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Psychosocial Interventions

APA recommends that patients with schizophrenia who are experiencing a first episode of psychosis be treated in a coordinated specialty care program.* (1, B)
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APA recommends that patients with schizophrenia be treated with cognitive-behavioral therapy for psychosis (CBTp).* (1, B)
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APA recommends that patients with schizophrenia receive psychoeducation.* (1, B)
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APA recommends that patients with schizophrenia receive supported employment services.* (1, B)
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APA recommends that patients with schizophrenia receive assertive community treatment if there is a history of poor engagement with services leading to frequent relapse or social disruption (e.g., homelessness; legal difficulties, including imprisonment).* (1, B)
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APA suggests that patients with schizophrenia who have ongoing contact with family receive family interventions.* (2, B)
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APA suggests that patients with schizophrenia receive interventions aimed at developing self-management skills and enhancing person-oriented recovery.* (2, C)
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APA suggests that patients with schizophrenia receive cognitive remediation.* (2, C)
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APA suggests that patients with schizophrenia who have a therapeutic goal of enhanced social functioning receive social skills training.* (2, C)
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APA suggests that patients with schizophrenia be treated with supportive psychotherapy.* (2, C)
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* This guideline statement should be implemented in the context of a person-centered treatment plan that includes evidence-based nonpharmacological and pharmacological treatments for schizophrenia.

Antipsychotic medications: available oral and short-acting intramuscular formulations*

Antipsychotic medications: available oral and short-acting intramuscular formulations*

Generic name
Trade name
(most common in U.S., may change)
Metabolic enzymes/
transporters
Available U.S. formulations
(mg, unless otherwise noted)
Initial dose
(mg/day)
Typical dose range
(mg/day)
Maximum daily dose
(mg/day)
First-generation antipsychotics
Chlorpromazine
Thorazine
CYP2D6 (Major), CYP1A2 (Minor), CYP3A4 (Minor) substrate Tablet: 10, 25, 50, 100, 200
Short-acting injection (HCl): 25/mL (1 mL, 2 mL)
25–100 200–800 Oral: 1000–2000
Fluphenazine
Prolixin
CYP2D6 (Major) substrate Tablet: 1, 2.5, 5, 10
Oral concentrate: 5/mL (120 mL)
Elixir: 2.5/5 mL (60 mL)
Short-acting injection (HCl): 2.5/mL (10 mL)
2.5–10 6–20 Oral: 40
IM: 10
Haloperidol
Haldol
CYP2D6 (Major), CYP3A4 (Major), CYP1A2 (Minor) substrate; 50-60% glucuronidation Tablet: 0.5, 1, 2, 5, 10, 20
Oral concentrate: 2/mL (5 mL, 15 mL, 120 mL)
Short-acting injection (lactate): 5/mL (1 mL, 10 mL)
1–15 5–20 Oral: 100
IM: 20
Loxapine
Loxitane
CYP1A2 (Minor), CYP2D6 (Minor), CYP3A4 (Minor) substrate; P-glycoprotein inhibitor Capsule: 5, 10, 25, 50
Aerosol powder breath-activated inhalation: 10
20 60–100a Oral: 250
Aerosol: 10
Molindone
Moban
CYP2D6 substrate Tablet: 5, 10, 25 50–75 30–100a 225
Perphenazine
Trilafon
CYP2D6 (Major), CYP1A2 (Minor), CYP2C19 (Minor), CYP2C9 (Minor), CYP3A4 (Minor) substrate Tablet: 2, 4, 8, 16 8–16 8–32 64
Pimozide
Orap
CYP1A2 (Major), CYP2D6 (Major), CYP3A4 (Major) substrate Tablet: 1, 2 0.5–2 2–4 10
Thioridazine
Mellaril
CYP2D6 (Major) substrate and moderate inhibitor, CYP2C19 (Minor) substrate Tablet: 10, 25, 50, 100 150–300 300–800a 800
Thiothixene
Navane
CYP1A2 (Major) substrate Capsule: 1, 2, 5, 10 6–10 15–30 60
Trifluoperazine
Stelazine
CYP1A2 (Major) substrate Tablet: 1, 2, 5, 10 4–10 15–20 50
Second-generation antipsychotics
Aripiprazole
Abilify
CYP2D6 (Major), CYP3A4 (Major) substrate Tablet: 2, 5, 10, 15, 20, 30
Tablet, disintegrating: 10, 15
Tablet with ingestible event marker (Mycite): 2, 5, 10, 15, 20, 30
Solution: 1/mL (150 mL)
10–15 10–15 30
Asenapine
Saphris
CYP1A2 (Major), CYP2D6 (Minor), CYP3A4 (Minor) substrate; glucuronidation by UGT1A4; CYP2D6 weak inhibitor Tablet, sublingual: 2.5, 5, 10 10 20 20
Asenapine
Secuado
CYP1A2 (Major), CYP2D6 (Minor), CYP3A4 (Minor) substrate; glucuronidation by UGT1A4; CYP2D6 weak inhibitor Transdermal system: 3.8 mg/24 hours, 5.7 mg/24 hours, 7.6 mg/24 hours 3.8 3.8–7.6 7.6
Brexpiprazole
Rexulti
CYP3A4 (Major), CYP2D6 (Major) substrate Tablet: 0.25, 0.5, 1, 2, 3, 4 1 2–4 4
Cariprazine
Vraylar
CYP3A4 (Major), CYP2D6 (Minor) substrate Capsule: 1.5, 3, 4.5, 6 1.5 1.5–6 6b
Clozapinec
Clozaril, FazaClo, Versacloz
CYP1A2 (Major), CYP2A6 (Minor), CYP2C19 (Minor), CYP2C9 (Minor), CYP2D6 (Minor), CYP3A4 (Minor) substrate Tablet: 25, 50, 100, 200
Tablet, disintegrating: 12.5, 25, 100, 150, 200
Oral suspension: 50/mL (100 mL)
12.5–25 300–450d 900
Iloperidone
Fanapt
CYP2D6 (Major), CYP3A4 (Minor) substrate, CYP3A4 weak inhibitor Tablet: 1, 2, 4, 6, 8, 10, 12 2 12–24 24
Lurasidone
Latuda
CYP3A4 (Major) substrate, CYP3A4 weak inhibitor Tablet: 20, 40, 60, 80, 120 40 40–120 160
Olanzapine
Zyprexa
CYP1A2 (Major), CYP2D6 (Minor) substrate; metabolized via direct glucuronidation Tablet: 2.5, 5, 7.5, 10, 15, 20
Tablet, disintegrating: 5, 10, 15, 20
Short-acting IM powder for solution: 10/2 mL
5–10 10–20 20e
Paliperidone
Invega
P-glycoprotein/
ABCB1, CYP2D6 (Minor), CYP3A4 (Minor) substrate
Tablet, extended release: 1.5, 3, 6, 9 6 3–12 12
Quetiapine
Seroquel
CYP3A4 (Major), CYP2D6 (Minor) substrate Tablet, immediate release: 25, 50, 100, 200, 300, 400
Tablet, extended release: 50, 150, 200, 300, 400
Immediate release: 50
Extended release: 300
400–800 800
Risperidone
Risperdal
CYP2D6 (Major), CYP3A4 (Minor), P-glycoprotein/
ABCB1 substrate, N-dealkylation (minor), CYP2D6 weak inhibitor
Tablet: 0.25, 0.5, 1, 2, 3, 4
Tablet, disintegrating: 0.25, 0.5, 1, 2, 3, 4
Oral solution: 1/mL (30 mL)
2 2–8 8f
Ziprasidone
Geodon
CYP1A2 (Minor), CYP3A4 (Minor) substrate, glutathione, aldehyde oxidase Capsule: 20, 40, 60, 80 Solution reconstituted, IM: 20 40 80–160 320
* This table includes information compiled from multiple sources. Detailed information on such issues as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.
a Usually given in divided doses.
b Up to 9 mg/day has been studied in clinical trials.
Clozapine levels should be drawn after at least 3 days on a stable dose and about 12 hours after the last dose. Levels associated with efficacy show individual variation, but efficacy typically begins at a level above 250 ng/mL, with the most efficacy seen at levels higher than 350 ng/mL. U.S. prescribers must complete Clozapine cREMS education (https://www.clozapinerems.com/) and follow requirements for a baseline CBC and ANC, and for ANC monitoring before and during treatment. Refer to clozapine labeling for detailed instructions on dose titration and dose adjustments with CYP450 interactions.
d May be taken without regard to food or other medications unless specifically noted.
e Olanzapine has been used at higher dosages, typically up to 30 mg/day, although some case series describe use of up to 60 mg/day.
f Dosages of risperidone up to 16 mg/day have been studied in clinical trials. However, doses >6 mg for twice-daily dosing do not appear to confer additional benefit and have a higher incidence of extrapyramidal symptoms than do lower doses.

Antipsychotic medications: relative side effects of oral formulations

Antipsychotic medications: relative side effects of oral formulations

Generic name Akathisia Parkinsonism Dystonia Tardive dyskinesia
First-generation antipsychotics
Chlorpromazine ++ ++ ++ +++
Fluphenazine +++ +++ +++ +++
Haloperidol +++ +++ +++ +++
Loxapine ++ ++ ++ ++
Molindone ++ ++ ++ ++
Perphenazine ++ ++ ++ ++
Pimozide +++ +++ ++ +++
Thioridazine + + + +
Thiothixene +++ +++ +++ +++
Trifluoperazine ++ ++ ++ ++
Second-generation antipsychotics
Aripiprazole ++ + + +
Asenapine ++ + ++ ++
Brexpiprazole ++ + + +
Cariprazine ++ + + +
Clozapine + + + +
Iloperidone + + + +
Lurasidone ++ ++ ++ ++
Olanzapine ++ ++ + +
Paliperidone ++ ++ ++ ++
Quetiapine + + + +
Risperidone ++ ++ ++ ++
Ziprasidone ++ + + +
Generic name Hyperprolactinemia a Anticholinergic Sedation
First-generation antipsychotics
Chlorpromazine + +++ +++
Fluphenazine +++ + +
Haloperidol +++ + +
Loxapine ++ ++ ++
Molindone ++ + ++
Perphenazine ++ ++ ++
Pimozide +++ + +
Thioridazine ++ +++ +++
Thiothixene +++ + +
Trifluoperazine ++ ++ +
Second-generation antipsychotics
Aripiprazole + + +
Asenapine ++ + ++
Brexpiprazole + + ++
Cariprazine + ++ ++
Clozapine + +++ +++
Iloperidone ++ + ++
Lurasidone + + ++
Olanzapine ++ ++ +++
Paliperidone +++ + +
Quetiapine + ++ +++
Risperidone +++ + ++
Ziprasidone ++ + ++
Generic name Seizures Orthostasis QT prolongation Weight gain
First-generation antipsychotics
Chlorpromazine ++ +++ +++ ++
Fluphenazine + + ++ ++
Haloperidol + + ++ ++
Loxapine + ++ ++ +
Molindone + + ++ +
Perphenazine + ++ ++ ++
Pimozide +++ + +++ +
Thioridazine ++ +++ +++ ++
Thiothixene +++ + ++ +
Trifluoperazine + + ++ ++
Second-generation antipsychotics
Aripiprazole + + + +
Asenapine + ++ ++ ++
Brexpiprazole + + ++ +
Cariprazine + + ++ ++
Clozapine +++ +++ ++ +++
Iloperidone + +++ +++ ++
Lurasidone + + + +
Olanzapine ++ ++ ++ +++
Paliperidone + ++ ++ ++
Quetiapine ++ ++ ++ ++
Risperidone + ++ ++ ++
Ziprasidone + ++ +++ +
Generic name Hyperlipidemia Glucose abnormalities Comments
First-generation antipsychotics
Chlorpromazine + ++
Fluphenazine + +
Haloperidol + +
Loxapine + +
Molindone + +
Perphenazine + +
Pimozide + +
Thioridazine + + b
Thiothixene + +
Trifluoperazine + +
Second-generation antipsychotics
Aripiprazole + + c
Asenapine ++ ++ d
Brexpiprazole ++ +
Cariprazine + +
Clozapine +++ +++ e
Iloperidone + ++
Lurasidone ++ ++ f
Olanzapine +++ +++
Paliperidone ++ +
Quetiapine +++ ++
Risperidone + ++ g
Ziprasidone + +
+=seldom; ++=sometimes; +++=often
a In general, rates of sexual dysfunction parallel rates of hyperprolactinemia except where noted in comments.
Pigmentary retinopathy; high rates of sexual dysfunction; avoid use if bQTc interval is >450 msec or with concomitant use of drugs that prolong the QTc interval or inhibit CYP2D6
c FDA safety alert for impulse control disorders (e.g., gambling, binge eating); may reduce hyperprolactinemia with other antipsychotics
d Oral hypoesthesia
e Increased salivation common; high rate of sexual dysfunction; severe constipation and paralytic ileus possible; fever can occur with initiation; myocarditis is infrequent; cardiomyopathy and severe neutropenia are rare
f Dose-related creatinine increase in some patients
g Intraoperative floppy iris syndrome reported

Long-acting injectable antipsychotic medications: dosing*

Long-acting injectable antipsychotic medications: dosing*

Generic name Trade name Dose conversions Initial dose (mg) Typical dose(mg) Maximum dose(mg) Dosing frequency Need for initial oral supplementation
First-generation antipsychotics
Fluphenazine Prolixin Decanoate For each 10 mg/day oral, give 12.5 mg decanoate every 3 weeks 6.25–25 every 2 weeks 6.25–25 every 2–4 weeks 100 2–4 weeks Decrease oral dose by half after first injection, then discontinue with second injection
Haloperidol Haldol decanoate For each 5 mg/day oral, give 50–75 mg decanoate every 4 weeks Determined by oral dose and/or risk of relapse up to a maximum of 100 mg 50–200 (10–15 times previous oral dose) 450/month 4 weeks Taper and discontinue after two to three injections
Second-generation antipsychotics
Aripiprazole monohydrate Abilify Maintena Not applicable 400 400 400/month Monthly Continue oral for 14 days after initial injection
Aripiprazole lauroxil Aristada Initio Not applicable 675 675 675 Single dose to initiate Aristada treatment or reinitiate treatment after a missed Aristada dose. Not for repeated dosing. Must be administered in conjunction with one 30 mg dose of oral aripiprazole.
Aripiprazole lauroxil Aristada 10 mg/day orally, give
441 mg IM/month
15 mg/day orally, give
662 mg/month IM,
882 mg IM every 6
weeks, or 1,064 mg
IM every 2 months
20 mg/day or greater
orally, give 882 mg/
month IM
Monthly: 441, 662,
882
Every 6 weeks: 882
Every 2 months:
1,064
Monthly:
441, 662, 882
Every 6 weeks:
882
Every 2 months:
1,064
882/month Monthly:
441, 662, 882
Every 6 weeks:
882
Every 2 months:
1,064
There are two ways to
initiate treatment:
1. Give one IM injection
of Aristada Initio
675 mg and
one dose of oral
aripiprazole 30
mg, or
2. Give 21 days of
oral aripiprazole in
conjunction with
the first Aristada
injection
Olanzapine Zyprexa Relprevv 10 mg/day orally, 210
mg every 2 weeks
for four doses, or
405 mg every 4
weeks
15 mg/day orally, 300
mg every 2 weeks
for four doses
20 mg/day orally, 300
mg every 2 weeks
Determined by oral dose 150 mg, 210 mg, or 300 mg every 2 weeks or 300 mg or 405 mg every 4 weeks 300 mg
every 2 weeks or 405 mg every 4 weeks
2–4 weeks Not required
Paliperidone palmitate Invega Sustenna 3 mg oral paliperidone, give 39–78 mg IM 6 mg oral, give 117 mg IM 9 mg, oral give 156 mg IM 12 mg oral, give 234 mg IM 234 mg IM on day 1 and 156 mg IM 1 week later, both administered in the deltoid muscle 78–234 mg monthly beginning at week 5 234 mg/ month Monthly Not required
Paliperidone palmitate Invega Trinza Conversion from monthly Invega Sustenna to every 3-month injections of Invega Trinza: 78 mg, give 273 mg 117 mg, give 410 mg 156 mg, give 546 mg 234 mg, give 819 mg Dependent on last dose of monthly paliperidone 273–819 819/3 months Every 3 months Not applicable
Risperidone Risperdal Consta Oral risperidone to Risperidone Consta IM: ≤3 mg/day, give 25 mg/2 weeks >3 to ≤5 mg/day, give 37.5 mg/2 weeks >5 mg/day, give 50 mg/2 weeks 25 every 2 weeks 25–50 every 2 weeks 50 every 2 weeks 2 weeks Continue oral for 3 weeks (21 days)
Risperidone Perseris Oral risperidone to subcutaneous risperidone extended release: 3 mg/day, give 90 mg/monthly 4 mg/day, give 120 mg/monthly Determined by oral dose 90–120 monthly 120/month Monthly Neither a loading dose nor oral overlap is needed
* This table includes information compiled from multiple sources. Detailed information on such issues as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.

Reversible inhibitors of human vesicular monoamine transporter type 2a

Reversible inhibitors of human vesicular monoamine transporter type 2a

Reversible inhibitors of human vesicular monoamine transporter type 2a
Genric name Deutetrabenazine Tetrabenazine Valbenazine
Trade name Austedo Xenazine Ingrezza
Available formulations (mg) Tablet: 6, 9, 12 Tablet: 12.5, 25 Capsule: 40, 80
Typical dose range (mg/day) 12–48 25–75 40–80
Bioavailability 80% 75% 49%
Time to peak level (hours) 3–4 1–2 0.5–1
Protein binding 60% to 68% (alpha-HTBZ) 59% to 63% (beta-HTBZ) 82% to 85% 60% to 68% (alpha-HTBZ) 59% to 63% (beta-HTBZ) >99% 64% alpha-HTBZ
Metabolism Hepatic Hepatic Hepatic
Metabolic enzymes/ transporters Major substrate of CYP2D6, minor substrate of CYP1A2 and CYP3A4 Major substrate of CYP2D6 Major substrate of CYP3A4, minor substrate of CYP2D6
Metabolites Deuterated alpha and beta HTBZ: Active Alpha, beta and O-dealkylated HTBZ: Active alpha- HTBZ: Active
Elimination half-life (hours) Deuterated alpha and beta HTBZ: 9–10 Alpha-HTBZ: 4–8 Beta-HTBZ: 2–4 15-22
Excretion Urine (~75%-85% changed); feces (~8%–11%) Urine (~75% changed); feces (~7%–16%) Urine: 60%; feces: 30%
Hepatic impairment Contraindicated Contraindicated Maximum dose of 40 mg daily with moderate to severe impairment (Child-Pugh score 7–15)
Renal impairment No information available No information available Use not recommended in severe renal impairment (CrCl <30 mL/min)
Common adverse effect Sedation Sedation, depression, extrapyramidal effects, insomnia, akathisia, anxiety, nausea, falls Sedation
Effect of food on bioavailability Food effects maximal concentration. Administer with food. Swallow tablets whole and do not chew, crush, or break. Unaffected by food Can be taken with or without food. High fat meals decreased the Cmax and AUC for valbenazine but values for the active metabolite (alpha-HTBZ) are unchanged
a This table includes information compiled from multiple sources. Detailed information on issues such as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.

Medications for treatment of medication-induced parkinsonisma

Medications for treatment of medication-induced parkinsonisma

Medications for treatment of medication-induced parkinsonisma
Genric name Amantadine Benztropine mesylate Diphenhydramine Trihexyphenidyl hydrochloride
Trade name Symmetrel Cogentin Benadryl Artane
Mechanism of action Uncompetitive NMDA receptor antagonist (weak) Muscarinic antagonist Histamine H1 antagonist Muscarinic antagonist
Available formulations (mg, unless otherwise noted) Tablet: 100 Tablet, extended release: 129, 193, 258
Capsule: 100 Capsule, liquid filled: 100 Capsule, extended release: 68.5, 137
Oral syrup: 50/5 mL
Tablet: 0.5, 1, 2 Solution, injection: 1/mL (2 mL) Capsule: 25, 50 Oral elixir: 12.5/5 mL Oral solution: 12.5/5 mL, 6.25/1 mL Tablet: 25, 50 Solution, injection: 50/1 mL Other brand name formulations are available for allergy relief Oral elixir: 0.4/mL (473 mL) Tablet: 2, 5
Typical dose range (mg/day) Immediate release tablet or capsule: 100–300
Extended release tablet: 129–322
Tablet: 0.5–6.0 Solution, injection: 1–2 Oral: 75–200 Solution, injection: 10–50 Oral: 5–15
Bioavailability 86%–94% 29% 40%–70% 100%
Time to peak level (hours) Immediate release: 2–4
Extended release: 7.5–12
Oral: 7
IM: minutes
1–4 1.3
Protein binding 67% 95% 76%–85% Not known
Metabolism Primarily renal Hepatic Hepatic Not known
Metabolic enzymes/ transporters Substrate of organic cation transporter 2 Substrate of CYP2D6 (minor) Extensively hepatic N-demethylation via CYP2D6; minor demethylation via CYP1A2, CYP2C9 and CYP2C19; inhibits CYP2D6 (weak) None known
Metabolites Multiple; unknown activity Not known Inactive Not known
Elimination half-life (hours) 16–17 7 4–8 4
Excretion Urine 85% unchanged; 0.6% fecal Urine Urine (as metabolites and unchanged drug) Urine and bile
Hepatic impairment No dose adjustments noted in labeling No dose adjustments noted in labeling No dose adjustments noted in labeling No dose adjustments noted in labeling
Renal impairment Elimination half-life increases with renal impairment No dose adjustments noted in labeling No dose adjustments noted in labeling. However, dosing interval may need to be increased or dosage reduced in older individuals and those with renal impairments. No dose adjustments noted in labeling
Comments Negligible removal by dialysis; do not crush or divide extended release products Onset of action with IV dose is comparable to IM Total daily dose typically divided into 3–4 doses per day.
Maximum daily dose 300 mg for oral and 400 mg for IM/IV, with 100 mg maximum dose for IV/IM.
Give IV dose at a rate of 25 mg/minute. Give IM dose by deep intramuscular injection because subcutaneous or intradermal injection can cause necrosis.
a This table includes information compiled from multiple sources. Detailed information on such issues as dose regimen, dose adjustments, medication administration procedures, handling precautions, and storage can be found in product labeling. It is recommended that readers consult product labeling information for authoritative information on these medications.

Recommendation Grading

Abbreviations

  • AIMS: Abnormal Involuntary Movement Scale
  • ANC: Absolute Neutrophil Count
  • AUC: Area Under The Curve
  • BMI: Body Mass Index (kg/m2)
  • CBC: Complete Blood Cell Count
  • CBTp: Cognitive-behavioral Therapy For Psychosis
  • CT: Computed Tomography
  • CYP: Cytochrome P450
  • Cmax: Maximum Plasma Concentration
  • DISCUS: Dyskinesia Identification System-Condensed User Scale
  • EEG: Electroencephalogram
  • HCI: Hydrochloride
  • HTBZ: Dihydrotetrabenazine
  • IM: Intramuscular
  • IV: Intravenous
  • LAI: Long -acting Injectable
  • MRI: Magnetic Resonance Imaging
  • NMDA: N-methyl-D-aspartate
  • QTc: Corrected QT Interval
  • REMS: Risk Evaluation And Mitigation Strategy
  • TSH: Thyroid Stimulating Hormone
  • VMAT2: Vesicular Monoamine Transporter 2

Disclaimer

This pocket guide attempts to define principles of practice that should produce high-quality patient care. It is applicable to specialists, primary care, and providers at all levels. This pocket guide should not be considered exclusive of other methods of care reasonably directed at obtaining the same results. The ultimate judgment concerning the propriety of any course of conduct must be made by the clinician after consideration of each individual patient situation. Neither IGC, the medical associations, nor the authors endorse any product or service associated with the distributor of this clinical reference tool.